Variant 20-34850032-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_178026.3(GGT7):c.1754G>A(p.Arg585Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000595 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

GGT7
NM_178026.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

GGT7 (HGNC:4259): (gamma-glutamyltransferase 7) This gene is a member of a gene family that encodes enzymes involved in both the metabolism of glutathione and in the transpeptidation of amino acids. Changes in the activity of gamma-glutamyltransferase may signal preneoplastic or toxic conditions in the liver or kidney. The protein encoded by this gene consists of a heavy and a light chain, and it can interact with CT120, a plasma membrane-associated protein that is possibly involved in lung carcinogenesis. [provided by RefSeq, Jul 2008]

GGT7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033757567).

BS2

High AC in GnomAd at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGT7	NM_178026.3 linkuse as main transcript	c.1754G>A	p.Arg585Gln	missense_variant	14/15	ENST00000336431.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGT7	ENST00000336431.10 linkuse as main transcript	c.1754G>A	p.Arg585Gln	missense_variant	14/15	1	NM_178026.3	P1	Q9UJ14-1
GGT7	ENST00000470952.2 linkuse as main transcript	c.*157G>A		3_prime_UTR_variant	3/3	5
GGT7	ENST00000469018.5 linkuse as main transcript	c.*60G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000883

AC:

AN:

249190

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461514

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000348

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000367

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00103

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000827

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.1754G>A (p.R585Q) alteration is located in exon 14 (coding exon 14) of the GGT7 gene. This alteration results from a G to A substitution at nucleotide position 1754, causing the arginine (R) at amino acid position 585 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.049

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.019

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0059

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.12

MutationTaster

Benign

0.67

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.15

REVEL

Benign

0.065

Sift

Benign

0.35

Sift4G

Benign

0.18

Polyphen

0.0020

Vest4

0.18

MVP

0.082

MPC

0.34

ClinPred

0.032

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over